PMID- 27494853 OWN - NLM STAT- MEDLINE DCOM- 20180220 LR - 20201209 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 35 DP - 2016 Aug 30 TI - Met promotes the formation of double minute chromosomes induced by Sei-1 in NIH-3T3 murine fibroblasts. PG - 56664-56675 LID - 10.18632/oncotarget.10994 [doi] AB - BACKGROUND: Sei-1 is an oncogene capable of inducing double minute chromosomes (DMs) formation. DMs are hallmarks of amplification and contribute to oncogenesis. However, the mechanism of Sei-1 inducing DMs formation remains unelucidated. RESULTS: DMs formation significantly increased during serial passage in vivo and gradually decreased following culture in vitro. micro nuclei (MN) was found to be responsible for the reduction. Of the DMs-carrying genes, Met was found to be markedly amplified, overexpressed and highly correlated with DMs formation. Inhibition of Met signaling decreased the number of DMs and reduced the amplification of the DMs-carrying genes. We identified a 3.57Mb DMs representing the majority population, which consists of the 1.21 Mb AMP1 from locus 6qA2 and the 2.36 Mb AMP2 from locus 6qA2-3. MATERIALS AND METHODS: We employed NIH-3T3 cell line with Sei-1 overexpression to monitor and characterize DMs in vivo and in vitro. Array comparative genome hybridization (aCGH) and fluorescence in situ hybridization (FISH) were performed to reveal amplification regions and DMs-carrying genes. Metaphase spread was prepared to count the DMs. Western blot and Met inhibition rescue experiments were performed to examine for involvement of altered Met signaling in Sei-1 induced DMs. Genomic walking and PCR were adopted to reveal DMs structure. CONCLUSIONS: Met is an important promotor of DMs formation. FAU - Bao, Yantao AU - Bao Y AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Liu, Jia AU - Liu J AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - You, Jia AU - You J AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Wu, Di AU - Wu D AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Yu, Yang AU - Yu Y AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. AD - Department of Genetics and Eugenics, Maternity and Child Care Center of Qinghuangdao, Qinghuangdao, China. FAU - Liu, Chang AU - Liu C AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Wang, Lei AU - Wang L AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. AD - Genetic Diagnosis Center, First People's Hospital of Yunnan Province, Yunnan, China. FAU - Wang, Fei AU - Wang F AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Xu, Lu AU - Xu L AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Wang, Liqun AU - Wang L AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Wang, Nan AU - Wang N AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Tian, Xing AU - Tian X AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Wang, Falin AU - Wang F AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Liang, Hongbin AU - Liang H AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Gao, Yating AU - Gao Y AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Cui, Xiaobo AU - Cui X AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Ji, Guohua AU - Ji G AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Bai, Jing AU - Bai J AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Yu, Jingcui AU - Yu J AD - Scientific Research Centre, Second Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Meng, Xiangning AU - Meng X AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Jin, Yan AU - Jin Y AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Sun, Wenjing AU - Sun W AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Guan, Xin-Yuan AU - Guan XY AD - Department of Clinical Oncology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China. AD - State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. FAU - Zhang, Chunyu AU - Zhang C AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. FAU - Fu, Songbin AU - Fu S AD - Laboratory of Medical Genetics, Harbin Medical University, Harbin, China. AD - Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions, Harbin, China. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Nuclear Proteins) RN - 0 (Sertad1 protein, mouse) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - EC 2.3.2.27 (Mdm2 protein, mouse) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Animals MH - Cell Nucleus MH - Cell Transformation, Neoplastic MH - Chromosome Aberrations MH - Chromosomes/*ultrastructure MH - Comparative Genomic Hybridization MH - Gene Amplification MH - Genome MH - In Situ Hybridization, Fluorescence MH - Metaphase MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Micronucleus Tests MH - NIH 3T3 Cells MH - Nuclear Proteins/*genetics MH - Oncogenes MH - Proto-Oncogene Proteins c-mdm2/genetics MH - Proto-Oncogene Proteins c-met/*genetics MH - *Signal Transduction MH - Trans-Activators/*genetics MH - Transcription Factors PMC - PMC5302943 OTO - NOTNLM OT - DMs OT - Sei-1 OT - amplification OT - in vivo passage OT - met COIS- The authors declare No potential conflicts of interest. EDAT- 2016/08/06 06:00 MHDA- 2018/02/21 06:00 PMCR- 2016/08/30 CRDT- 2016/08/06 06:00 PHST- 2016/03/30 00:00 [received] PHST- 2016/07/19 00:00 [accepted] PHST- 2016/08/06 06:00 [pubmed] PHST- 2018/02/21 06:00 [medline] PHST- 2016/08/06 06:00 [entrez] PHST- 2016/08/30 00:00 [pmc-release] AID - 10994 [pii] AID - 10.18632/oncotarget.10994 [doi] PST - ppublish SO - Oncotarget. 2016 Aug 30;7(35):56664-56675. doi: 10.18632/oncotarget.10994.